Grant Number:
Principal Investigator:
Chen, Yu
Institution:
New York University
Most Recent Award Year:
2009
Lifestage of Participants:
Exposure:
Adulthood (18+ years)
Assessment:
Adulthood (18+ years)
Exposures:
Metals:
Arsenic
Health Outcomes:
Cardiovascular Outcomes:
Cardiovascular disease; Coronary artery disease
Biological Sample:
Serum; Urine
Environmental Sample:
Drinking water sample
Other Participant Data:
Intima-medial thickness as measure of atherosclerosis
Genes or Other DNA Products Studied:
Genes related to arsenic methylation (GSTM1, GSTT1, GSTO1, GSTP1, MTHFR, and AS3MT genes), oxidative stress (NOS3, SOD2, and CYBA), and inflammation and endothelial dysfunction (TNF, IL6, ICAM1, and VCAM1)
Abstract:
Cardiovascular disease (CVD) is the leading cause of death worldwide. Recent experimental studies support the hypothesis that As exposure leads to oxidative stress and vascular inflammation, a central mechanism to the development of atherosclerosis and CVD. Studies of other health effects of As exposure have suggested effect-modification by As methylation capacity and genetic susceptibility. However, epidemiologic studies of genetic susceptibility to the effects of As exposure on CVD risk are lacking. In the year 2000, we established the Health Effects of Arsenic Longitudinal Study (HEALS), a prospective cohort study of 11,746 participants (original cohort), in Araihazar, Bangladesh. In 2007, HEALS recruited another 8,288 participants (expansion cohort) to include a total of 20,034 participants. More than 90% of the cohort have exposed to As exposure at low-to-moderate levels (<300 5g/L), providing us with a unique opportunity to assess health effects of As exposure from drinking water at the levels of public health interest. As part of the parent study, cardiovascular outcomes of the cohort participants are being ascertained, and carotid artery intima-medial thickness (IMT) is being measured for 1,160 participants randomly selected from the original cohort. On the basis of these resources, our substantial pilot data, as well as cohort analyses which show a positive association between As exposure and CVD incidence and mortality, we propose a series of analyses to assess the genetic susceptibility to the effects of As exposure on the risk of atherosclerosis and CVD. We will evaluate whether the cardiovascular effects of As exposure differ by polymorphisms in genes related to As methylation (GSTM1, GSTT1, GSTO1, GSTP1, MTHFR, and AS3MT genes) and genes related to oxidative stress (NOS3, SOD2, and CYBA) and inflammation/endothelial dysfunction (TNF, IL6, ICAM1, and VCAM1) using a cross-sectional study of IMT with the subcohort of 1,160 participants, and a case-cohort study of CVD risk with 692 cases and the same subcohort of 1,160 participants from the original cohort. The strongest gene- As interaction will be tested again in a second case-cohort study with 305 cases and another subcohort of 520 participants selected from the expansion cohort. To further characterize the underlying mechanisms by which As exposure causes CVD, we will conduct a cross-sectional study with 300 subjects to evaluate the associations between As exposure and serum/urinary phenotypic markers for oxidative stress and inflammation. The proposed study will provide valuable knowledge about the pathophysiology and mechanism by which As exposure may lead to CVD and may also lead to improved prevention and risk assessment of As exposure.
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Related NIEHS-Funded Study Populations
Health Effects of Arsenic Longitudinal Study (HEALS)
Principal Investigator:
Ahsan, Habibul; Graziano, Joseph
| Study Population Page Study Population c63
Institution:
University of Chicago
Location:
Araihazar, Bangladesh
Number of Participants::
~35,000 recruited; Recruitment goal of 50,000
Brief Description::
This large prospective cohort study is based on individual-level data from a population exposed to a wide range of inorganic arsenic from drinking water in Araihazar, Bangladesh. Since 2000, the study has recruited more than 35,000 men and women with extensive questionnaire data, biological samples, drinking water samples, and diagnostic/clinical data.